Downregulation of CD4 is required for maintenance of viral infectivity of HIV-1
Downregulation of CD4 is required for maintenance of viral infectivity of HIV-1
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DOI：
10.1016/s0042-6822(03)00126-0
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发表时间：
2003-07-05
期刊：
影响因子：
3.7
通讯作者：
Sakai, H
中科院分区：
文献类型：
--
作者：
Tanaka, M;Ueno, T;Sakai, H
细胞表面病毒受体的下调被认为对于预防重复感染很重要。HIV-1编码多种基因产物Env、Vpu和Nef，参与下调CD 4（一种主要的HIV-1受体）。我们发现vpu和nef的同时突变严重损害了病毒的复制。我们研究了由Vpu和Nef介导的CD 4下调在病毒感染性修饰中的参与。vpu的突变增加了CD 4掺入病毒粒子而不影响其中的Env含量，抑制了病毒粒子与CD 4阳性细胞表面的附着步骤。虽然nef的单一突变通过CD 4非依赖性机制抑制病毒感染性，但它可以与vpu突变组合增加病毒粒子中的CD 4掺入。这些结果表明，CD 4下调是维持病毒粒子中Env功能所必需的。(C)2003 Elsevier Science（美国）。All rights reserved.
Downregulation of virus receptors on the cell surface is considered to be important in preventing superinfection. HIV-1 encodes multiple gene products, Env, Vpu, and Nef, involved in downregulation of CD4, a major HIV-1 receptor. We found that simultaneous mutations in both vpu and nef severely impaired virus replication. We examined the involvement of CD4 downregulation mediated by Vpu and Nef in the modification of virus infectivity. The mutation in vpu increased CD4 incorporation into virions without affecting the Env content in it, inhibiting the attachment step of virions to the CD4-positive cell surface. Although a single mutation in nef suppresses virus infectivity via a CD4-independent mechanism, it could augment CD4 incorporation in virions in combination with a vpu mutation. These results indicated that CD4 downregulation was necessary for maintenance of Env function in the virion. (C) 2003 Elsevier Science (USA). All rights reserved.